Our long-range goal is to acquire the ability to prevent or reverse human neoplasia, through clarification of the initial molecular events which underlie its appearance and progression. Our current objectives are to understand the molecular basis of two sets of cellular changes we have observed in vitro. The first is the series of hereditable changes in growth control of rodent cells brought on by persistent expression of the integrated transforming genes of the tumor virus SV40. The second is the series of phenotypic alterations in cultured skin fibroblasts brought on by human mutations which result in inherited colon carcinoma. Our hypothesis has been that these two sets of changes might be related in some way, for instance by being the consequence of similar gene functions. In the past two years our work and that of others has led us to conclude that these two series of cellular changes are indeed functionally very similar. To the extent that this is so, any advance in our understanding of either system becomes of immediate relevance to the other. Hence, pursuit of the genetic, physiological and molecular similarities between these two in vitro systems seems to us to be a sensible immediate objective, and experiments designed to do so are described in this application. Based on these and other results, we also plan to construct culture assays to analyze the later stages of neoplasia.